CTNND2

catenin delta 2, the group of Armadillo repeat containing|p120 catenin family

Basic information

Region (hg38): 5:10971835-11904446

Links

ENSG00000169862 ∙ NCBI:1501 ∙ OMIM:604275 ∙ HGNC:2516 ∙ Uniprot:Q9UQB3 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• benign adult familial myoclonic epilepsy (Supportive), mode of inheritance: AD
• complex neurodevelopmental disorder (Strong), mode of inheritance: AD

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the CTNND2 gene.

• not provided (184 variants)
• Inborn genetic diseases (41 variants)
• not specified (5 variants)
• CTNND2-related condition (3 variants)
• CTNND2-associated Neurodevelopmental syndrome (2 variants)
• Neurodevelopmental disorder (2 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CTNND2 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				17	10	27
missense		2	49	10	5	66
nonsense		3	1			4
start loss						0
frameshift		3	2			5
inframe indel			1	5	3	9
splice donor/acceptor (+/-2bp)		1	1			2
splice region			1	4	4	9
non coding			1	31	68	100
Total	0	9	55	63	86

Variants in CTNND2

This is a list of pathogenic ClinVar variants found in the CTNND2 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
5-10973451-C-T			Likely benign (Sep 29, 2020)
5-10973467-C-T		CTNND2-related disorder	Uncertain significance (Sep 19, 2022)
5-10973468-G-A		CTNND2-related disorder	Likely benign (Dec 31, 2019)
5-10973478-G-A		Inborn genetic diseases	Uncertain significance (Jan 19, 2024)
5-10973497-A-G		Inborn genetic diseases	Uncertain significance (Dec 28, 2023)
5-10973615-G-A			Benign (Jul 03, 2018)
5-10973669-G-A			Benign/Likely benign (Jan 13, 2021)
5-10973688-T-A		Inborn genetic diseases	Uncertain significance (Aug 17, 2021)
5-10973719-C-T		CTNND2-related disorder	Benign (Oct 27, 2021)
5-10973721-G-A			Benign/Likely benign (Dec 22, 2020)
5-10973815-T-C			Benign (Jul 03, 2018)
5-10973903-G-A			Benign (Jul 03, 2018)
5-10974028-C-T			Likely benign (Dec 12, 2018)
5-10974042-G-A			Benign (Jul 03, 2018)
5-10981481-G-A			Benign (Jul 03, 2018)
5-10981519-T-C			Benign (Aug 10, 2018)
5-10981539-T-C			Benign (Aug 10, 2018)
5-10981586-A-AAC			Benign (Aug 27, 2019)
5-10981586-A-AACAC			Likely benign (Jun 05, 2020)
5-10981586-A-AACACAC			Benign (Sep 19, 2019)
5-10981586-A-AACACACACAC			Benign (Feb 19, 2021)
5-10981608-G-C			Benign (Aug 20, 2019)
5-10981659-G-C			Benign (Aug 31, 2018)
5-10981672-GTTCT-G			Likely benign (Jan 28, 2019)
5-10981767-C-CTTTA			Benign (Aug 28, 2018)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CTNND2	protein_coding	protein_coding	ENST00000304623	22	932204

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	1.66e-9	125745	0	3	125748	0.0000119

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.77	489	695	0.704	0.0000418	7827
Missense in Polyphen		100	209.08	0.47829		2173
Synonymous	-1.27	334	306	1.09	0.0000204	2539
Loss of Function	7.21	2	64.4	0.0310	0.00000352	692

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000266	0.0000264
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Has a critical role in neuronal development, particularly in the formation and/or maintenance of dendritic spines and synapses (PubMed:25807484). Involved in the regulation of Wnt signaling (PubMed:25807484). It probably acts on beta- catenin turnover, facilitating beta-catenin interaction with GSK3B, phosphorylation, ubiquitination and degradation (By similarity). Functions as a transcriptional activator when bound to ZBTB33 (By similarity). May be involved in neuronal cell adhesion and tissue morphogenesis and integrity by regulating adhesion molecules. {ECO:0000250|UniProtKB:O35927, ECO:0000269|PubMed:25807484, ECO:0000269|PubMed:9971746}.
• Disease: DISEASE: Note=Defects in CTNND2, including deleterious missense and copy number variants (CNVs) are involved in autism, a complex multifactorial, pervasive developmental disorder characterized by impairments in reciprocal social interaction and communication, restricted and stereotyped patterns of interests and activities, and the presence of developmental abnormalities by 3 years of age. Most individuals with autism also manifest moderate mental retardation. {ECO:0000269|PubMed:25807484}.
• Pathway: Ectoderm Differentiation (Consensus)

Recessive Scores

• pRec: 0.0936

Intolerance Scores

• loftool: 0.00475
• rvis_EVS: -2.41
• rvis_percentile_EVS: 1.07

Haploinsufficiency Scores

• pHI: 0.401
• hipred: Y
• hipred_score: 0.814
• ghis: 0.620

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.815

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Ctnnd2
• Phenotype: behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan)

Zebrafish Information Network

• Gene name: ctnnd2b
• Affected structure: post-vent region
• Phenotype tag: abnormal
• Phenotype quality: curved

Gene ontology

• Biological process: cell-cell junction assembly;cell adhesion;signal transduction;Wnt signaling pathway;synapse organization;regulation of canonical Wnt signaling pathway;dendritic spine morphogenesis;cell-cell adhesion
• Cellular component: nucleus;cytoplasm;plasma membrane;cell-cell junction;cell-cell adherens junction;postsynaptic density;dendrite;perikaryon
• Molecular function: protein binding;beta-catenin binding;cadherin binding